ANALYSIS OF HERMINAL MUTATIONS IN ONCOGENES AND TUMOR SUPPRESSOR GENES IN WOMEN WITH MULTIPLE PRIMARY MALIGNANT NEOPLASMS


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. Multiple primary malignant neoplasms (MPMN) most often develop in individuals with a hereditary predisposition to oncological diseases. There are inherited allelic variants of oncogenes, tumor suppressor genes and their combinations which disrupt the functional activity of the corresponding proteins. This leads to the development of certain tumors and is clinically manifested as familial oncological syndromes. Materials and methods. Fifty key genes associated with carcinogenesis were sequenced for 8 women, developed MPMN and have a family tumor history. Results. A total of 26 polymorphic variants were identified in l8 genes. Ten of them are located in introns, one - in the regulatory region of the gene, ten of them are silent-mutations, five - are missense-mutations. Each patient has from 9 to l7 such variants. Probably the polymorphism RET rsl800863 in the existing genomic context in Patient № l predetermined the development of medullary thyroid cancer in her and her daughter. Family of patient №2 shows a picture typical of Li-Fraumeni-like syndrome. We assume that due to either the single homozygous TP53 rsl800372 polymorphism, or its combination with TP53 rsl042522 polymorphism, determines the presence of Li-Fraumeni-like syndrome in this family. Conclusion. The frequency of rs55986963, rsl050l7l, rsl2628 polymorphisms in the sample exceeds that in the population. It is necessary to expand the sample at the expense of MPMN-patients and healthy women for further discussion.

Full Text

Restricted Access

About the authors

A. V Savkova

Federal Research Center of Fundamental and Translational Medicine»

Email: alivsesav@gmail.com
Novosibirsk, Russian Federation

A. V Gerasimov

Novosibirsk Regional Clinical Oncological Dispensary

Novosibirsk, Russian Federation

G. V Vasiliev

Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences

Novosibirsk, Russian Federation

S. E Krasilnikov

Novosibirsk Regional Clinical Oncological Dispensary

Novosibirsk, Russian Federation

L. F Gulyaeva

Federal Research Center of Fundamental and Translational Medicine»

Novosibirsk, Russian Federation

V. E Voitsitsky

Novosibirsk Regional Clinical Oncological Dispensary

Novosibirsk, Russian Federation

References

  1. Злокачественные новообразования в России в 2017 году (Заболеваемость и смертность), под ред. Каприна А.Д., Старинского В.В., Петровой ПВ. М., 2018; 250.
  2. Zhong R., Liu L., Zou L., Sheng W., Zhu B., Xiang H., Chen W., Chen J., Rui R., Zheng X., Yin J., Duan S., Yang B., Sun J., Lou J., Liu L., Xie D., Xu Y., Nie S., Miao X. Genetic variations in the TGF signaling pathway, smoking and risk of colorectal cancer in a Chinese population. Carcinogenesis. 2013; 34 (4): 936-42. https:// doi.org/10.1093/carcin/bgs395
  3. Figlioli G., Landi S., Romei C., Elisei R., Gemignani F. Medullary thyroid carcinoma (MTC) and RET proto-oncogene: Mutation spectrum in the familial cases and a metaanalysis of studies on the sporadic form. Mutat. Res. 2013; 752 (1): 36-44. https://doi. org/10.1016/j.mrrev.2012.09.002
  4. Machens A., Frank-Raue K., Lorenz K., Rondot S., Raue F., Dralle H. Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer. Clin Endocrinol (Oxf). 2012; 76 (5): 691-7. https:// doi.org/10.1111/j.1365-2265.2011.04293.x.
  5. Sheikholeslami S., Zarif Yeganeh M., Hoghooghi Rad L., Golab Ghadaksaz H., Hedayati M. Haplotype frequency of G691S/S904S in the RET proto-onco-gene in patients with medullary thyroid carcinoma. Iran J. Public Health. 2014; 43 (2): 235-40.
  6. Arneth B. G691S/S904S polymorphism in the RET protooncogene of a 25-year-old medical student with bilateral pheochromocytoma. Indian J. Hum Genet. 2009; 15 (1): 32-5. https://doi.org/10.4103/0971-6866.50868.
  7. Tomei S., Adams S., Uccellini L., Bedognetti D., De Giorgi V., Erdenebileg N., Ascierto M.L., Reinboth J., Liu Q., Bevilacqua G., Wang E., Mazzanti C., Marincola F.M. Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of melanoma in the North Am. population.
  8. Deben C., Van den Bossche J., Van Der Steen N., Lardon F, Wouters A., de Beeck K.O., Hermans C., Jacobs J., Peeters M., Van Camp G., Rolfo C., Deschoolmeester V, Pauwels P. Deep sequencing of the TP53 gene reveals a potential risk allele for nonsmall cell lung cancer and supports the negative prognostic value of TP53 variants. Tumour Biol. 2017; 39 (2): 1010428317694327. https://doi.org/10.1177/1010428317694327.
  9. Samuel N., Id Said B., Guha T, Novokmet A., Li W., Silwal-Pandit L., B0rrsen-Dale A.L., Langer0d A., Hudson T.J., Malkin D. Assessment of TP53 polymorphisms and MDM2 SNP309 in premenopausal breast cancer risk. Hum Mutat. 2017; 38 (3): 265-8. https:// doi.org/10.1002/humu.23154.
  10. Bilous N., Abramenko I., Saenko V., Chumak A., Dyagil I., Martina Z., Kryachok I. Clinical relevance of TP53 polymorphic genetic variations in chronic lymphocytic leukemia. Leuk Res. 2017; 58: 1-8. https:// doi.org/10.1016/j.leukres.2017.03.009.
  11. Mirabello L., Yeager M., Mai P.L., Gastier-Foster J.M., Gorlick R., Khanna C., Patino-Garcia A., Sierrasesumaga L., Lecanda F., Andrulis I.L., Wunder J.S., Gokgoz N., Barkauskas D.A., Zhang X., Vogt A., Jones K., Boland J.F., Chanock S.J., Savage S.A. Germline TP53 variants and susceptibility to osteosarcoma. J. Natl Cancer Inst. 2015; 107 (7): 101. https://doi.org/10.1093/jnci/djv101.
  12. Zhang J., Yang J., Chen Y., Mao Q., Li S., Xiong W., Lin Y., Chen J., Ge J. Genetic variants of VEGF (rs201963 and rs3025039) and KDR (rs7667298, rs2305948, and rs1870377) are associated with glioma risk in a han chinese population: a case-control study. Mol. Neurobiol. 2016; 53 (4): 2610-8. https:// doi.org/10.1007/s12035-015-9240-0.
  13. Agarwal D., Hatzis C., Pusztai L. Functional polymorphisms in cancer. Oncoscience. 2015; 2 (2): 73-4.
  14. Neklason D.W., Done M.W., Sargent N.R., Schwartz A.G., Anton-Culver H., Griffin C.A., Ahnen D.J., Schildkraut J.M., Tomlinson G.E., Strong L.C., Miller A.R., Stopfer J.E., Burt R.W. Activating mutation in Met oncogene in familial colorectal cancer. BMC Cancer. 2011; 11: 424. https://doi. org/10.1186/1471-2407-11-424.
  15. Liu S., Meric-Bernstam F., Parinyanitikul N., Wang B., Eterovic A.K., Zheng X., Gagea M., Chavez-MacGregor M., Ueno N.T., Lei X., Zhou W., Nair L., Tripathy D., Brown P.H., Hortobagyi G.N., Chen K., Mendelsohn J., Mills G.B., Gonzalez-Angulo A.M. Functional consequence of the MET-T1010I polymorphism in breast cancer. Oncotarget. 2015; 6 (5): 2604-14.
  16. Tian X., Dai S., Sun J., Jiang S., Jiang Y. Association between TP53 Arg72Pro polymorphism and leukemia risk: a meta-analysis of 14 case-control studies. Sci Rep. 2016. 7 (6): 24097. https://doi.org/10.1038/srep24097.
  17. Tian X., Dai S., Sun J., Jiang S., Jiang Y. The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies. Oncotarget. 2017; 8 (1): 1156-65. htt-ps://doi.org/10.18632/oncotarget.13589.
  18. Apsalikov B., Manambaeva Z., Ospanov E., Massabayeva M., Zhabagin K., Zhagiparova Z., Maximov V, Voropaeva E., Apsalikov K., Belikhina T, Abdrahmanov R., Cherepkova E., Tanatarov S., Massadykov A., Urazalina N. BRCA1 and TP53 gene-mutations: family predisposition and radioecological risk of developing breast cancer. Asian. Pac. J. Cance.r Prev 2016; 17 (8): 4059-62.
  19. Hu S., Zhao L., Yang J., Hu M. The association between polymorphism of P53 codon 72 Arg/Pro and hepatocellular carcinoma susceptibility: evidence from a metaanalysis of 15 studies with 3704 cases. Meta Gene. 2013; 1: 126-37. https://doi. org/10.1016/j.mgene.2013.09.010.
  20. Xi Y, Liu C., Xin X. Association Between a Single Nucleotide Polymorphism in the TP53 region and risk of ovarian cancer. Cell Biochem Biophys. 2014; 70 (3): 1907-12. https://doi.org/10.1007/s12013-014-0150-y.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies